OVERALL PROJECT SUMMARY/ABSTRACT Cardiovascular (CV), renal and metabolic diseases are inextricably linked and are the leading causes of mortality and morbidity in the U.S., especially in Mississippi which has the highest prevalence in the nation of these diseases. Cardiorenal and metabolic disorders usually cluster together and are highly interdependent. Obesity and associated metabolic disorders, such as diabetes, are major causes of CV and renal disease. Abnormal kidney function is an important cause as well as a consequence of hypertension, a key risk factor for CV diseases such coronary artery disease and stroke. Understanding the complex relationships among CV, renal, and metabolic disorders and developing new therapeutic approaches requires a paradigm shift in research that incorporates multidisciplinary integrated approaches, combining the efforts of basic, clinical and population scientists. A major objective of this Phase 2 COBRE proposal is to further develop a leading Cardiorenal and Metabolic Diseases Research Center (CMDRC) that brings together a multidisciplinary group of basic, clinical and population scientists working on a common synergistic theme, and to facilitate their collaborations. The specific aims are: 1) to further develop infrastructure and core facilities that foster excellence in basic, clinical, and population research in cardiorenal and metabolic diseases and increase competitiveness of CMDRC investigators for independent funding from NIH and other national biomedical research programs; 2) to enhance CMDRC mentoring and education programs and research support for promising new investigators so that they can become productive, independent investigators who are also effective collaborators on multidisciplinary research teams; 3) to achieve the specific aims of the research projects described by Junior Investigators in this proposal, and to foster their career development; 4) to further develop a pipeline of diverse postdoctoral fellows, graduate and undergraduate students trained in cutting edge cardiorenal and metabolic diseases research so they become the next generation of researchers in this field; major emphasis is placed on recruiting and mentoring underrepresented minority investigators through partnerships with local institutions and by leveraging training programs at UMMC; 5) to enhance collaborations and interactions among established investigators from multiple disciplines in cardiorenal and metabolic diseases at UMMC, other IDeA supported programs, and external partners; 6) to strengthen cardiorenal and metabolic disease research at UMMC by recruiting new faculty with expertise in clinical and translational research, and in emerging technologies (e.g. in vivo imaging, bioinformatics, and systems analysis) and in areas where there are gaps in CMDRC expertise.